Organization, evolution and functions of the human and mouse Ly6/uPAR family genes.

Chelsea L Loughner,Monica S Mcandrews,Shivalingappa K Swamynathan,Sudha Swamynathan,Emili E Delp,Elspeth A Bruford

doi:10.1186/s40246-016-0074-2

Chelsea L Loughner, Monica S Mcandrews + Show 4 more

Open Access

https://doi.org/10.1186/s40246-016-0074-2

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Abstract

Members of the lymphocyte antigen-6 (Ly6)/urokinase-type plasminogen activator receptor (uPAR) superfamily of proteins are cysteine-rich proteins characterized by a distinct disulfide bridge pattern that creates the three-finger Ly6/uPAR (LU) domain. Although the Ly6/uPAR family proteins share a common structure, their expression patterns and functions vary. To date, 35 human and 61 mouse Ly6/uPAR family members have been identified. Based on their subcellular localization, these proteins are further classified as GPI-anchored on the cell membrane, or secreted. The genes encoding Ly6/uPAR family proteins are conserved across different species and are clustered in syntenic regions on human chromosomes 8, 19, 6 and 11, and mouse Chromosomes 15, 7, 17, and 9, respectively. Here, we review the human and mouse Ly6/uPAR family gene and protein structure and genomic organization, expression, functions, and evolution, and introduce new names for novel family members.

Highlights

The lymphocyte antigen-6 (Ly6)/urokinase-type plasminogen activator receptor superfamily of structurally related proteins is characterized by the LU domain, an 80 amino acid domain containing ten cysteines arranged in a specific spacing pattern that allows distinct disulfide bridges which create the three-fingered (3F) structural motif [1, 2]
GPIanchored Ly6/urokinase-type plasminogen activator receptor (uPAR) family members tend to congregate on lipid rafts on the cell surface, which promotes their interactions with other proteins
Analysis of the phylogenetic relationship among human and mouse Ly6/uPAR family proteins revealed that (i) human LY6K and mouse GML2 are the most ancestral Ly6 proteins with the longest unbranched streak in these two species, (ii) human and mouse LYPD6 are the most recent addition to the family closely followed by mouse LY6C1 and LY6C2, (iii) most of the secreted family proteins form a separate cluster distinct from the GPIanchored proteins, and (iv) several mouse prostate and testis expressed (PATE) proteins (PATE4, 5, 6, 7, 8, 9, 10, 13, and 14) have long unbranched streaks suggesting that they have ancient origin and that the important function(s) that they serve have not changed much (Fig. 2)

Summary

Introduction

The lymphocyte antigen-6 (Ly6)/urokinase-type plasminogen activator receptor (uPAR) superfamily of structurally related proteins is characterized by the LU domain, an 80 amino acid domain containing ten cysteines arranged in a specific spacing pattern that allows distinct disulfide bridges which create the three-fingered (3F) structural motif [1, 2]. The fully annotated human and mouse genomes contain 35 and 61 Ly6/uPAR family members, respectively. GPIanchored Ly6/uPAR family members tend to congregate on lipid rafts on the cell surface, which promotes their interactions with other proteins.

Results

Conclusion